Bombesin- and CCK-related peptides are found widely in the gastrointestinal (GI) tract and central nervous system, however, aspects of their cellular basis of action remain unclear, particularly the role of tyrosine phosphorylation in their signaling cascade. During this year we have primarily focused on tyrosine phosphorylation cascades stimulated by activation of CCKA-R. In previous studies CCKA-R activation has been shown to be coupled to activation of phospholipase C with mobilization of cellular [Ca-2+], and activation of PKC, PLD, and PLA-2. Recent studies by us and others show that similar to growth factors, increased tyrosine phosphorylation by CCK may also be an important cellular cascade. We demonstrated CCKA-R causes tyrosine phosphorylation of p125 focal adhesion kinase, paxillin, p130-cas and the novel cytoplasmic tyrosine kinase, PYK2/CAKB. For each of these proteins we have determined the role of activation of phospholipase C with cellular [Ca2+]i mobilization and protein kinase C (PKC), as well as the importance of the small GTP binding protein, Rho in the tyrosine phosphorylation. We have recently extended these studies to investigate the ability of CCKA-R activation to stimulate tyrosine phosphorylation, of a PKC delta, a PKC isoform important in regulating cell growth and apoptosis. In recent studies we found CCKA-R activation causes rapid tyrosine phosphorylation of PKC delta, which is independent of changes in [Ca2+]i or PI-3K, but is reciprocally regulated by activation of PKC-alpha. These results show CCK activates both stimulating and inhibitory cascades to regulate PKC-delta tyrosine phosphorylation which is likely important in its effects on cell growth.